IKKalpha and IKKbeta specific inhibitors

Abstract

A method for modulating NF-κB dependent gene transcription in a cell comprised of modulating IKKα and IKKβ protein and protein activity in the cell. The present invention also provides siRNA compositions and methods thereof for modulating NF-κB dependent gene transcription.

1 . A purified siRNA sequence comprised of SEQ ID. No. 1.  
     
     
         2 . An expression vector that expresses the siRNA of  claim 1 .  
     
     
         3 . A retroviral vector that expresses the siRNA of  claim 1 .  
     
     
         4 . The retroviral vector of  claim 2  wherein the vector is comprised of a 5′ LTR, a selective gene, a polymerase III, RNA promoter and a 3′LTR.  
     
     
         5 . A purified siRNA sequence of SEQ ID. No. 3.  
     
     
         6 . A retroviral vector that expresses the siRNA of  claim 3 .  
     
     
         7 . The retroviral vector of  claim 6  wherein the vector is comprised of a 5′ LTR, a selective agent, promoter and a 3′LTR.  
     
     
         8 . A method for inhibiting the expression of NF-κB dependent genes, said method comprised of the steps of administering to a cell an IKKα specific inhibitor and an IKKβ specific inhibitor.  
     
     
         9 . The method of  claim 8  wherein the IKKα specific inhibitor is an siRNA targeted to the IKKα gene and the IKKβ specific inhibitor is an siRNA targeted to the IKKβ gene.  
     
     
         10 . The method of  claim 8  wherein the IKKα specific inhibitor and the IKKβ specific inhibitor are administered simultaneously.  
     
     
         11 . The method of  claim 8  wherein the IKKα specific inhibitor is administered first and then the IKKβ specific inhibitor administered second.  
     
     
         12 . The method of  claim 8  wherein the IKKβ specific inhibitor is administered first and then the IKKα specific inhibitor administered second.  
     
     
         13 . The method of  claim 11  wherein the specific inhibitor of IKKα is an siRNA and the specific inhibitor of IKKβ is an siRNA.  
     
     
         14 . The method of  claim 11  wherein the specific inhibitor of IKKα is the siRNA sequence of SEQ ID. No. 1.  
     
     
         15 . The method of  claim 11  wherein the specific inhibitor of IKKβ is the siRNA sequence of SEQ ID. No. 3.  
     
     
         16 . The method of  claim 11  wherein the specific inhibitor of IKKα is administered as a retroviral vector.  
     
     
         17 . The method of  claim 11  wherein the specific inhibitor of IKKβ is administered as a retroviral vector.  
     
     
         18 . A method for treating autoimmune and inflammatory disease in a patient in need thereof comprised of the steps of administration of an IKKα and an IKKβ specific inhibitor.  
     
     
         19 . The method of  claim 18  wherein the autoimmune and inflammatory disease is selected from the list consisting of asthma, multiple sclerosis, SLE, rheumatoid arthritis, inflammatory bowel disease, and psoriasis.  
     
     
         20 . The method of  claim 19  wherein said disease is asthma.  
     
     
         21 . The method of  claim 1  wherein said disease is SLE.  
     
     
         22 . The method of  claim 1  wherein said disease is cancer.  
     
     
         23 . A method for modulating NF-κB dependent gene transcription by administration of an IKKα specific inhibitor and an IKKβ specific inhibitor wherein the specific inhibitors are comprised of siRNA directed to IKKα and IKKβ cDNA sequences.  
     
     
         24 . The method of  claim 11  where the NF-κB dependent gene is chosen from IL-6, IL-8, IL-2,Cox-2, ICAM-1, VCAM-1, GM-CSF, tumor necrosis factor, Gro-1, Rantes, and serum amyloid A.  
     
     
         25 . The method according to  claim 11  where the NF-κB dependent gene is IL-6 or IL-8.